Effect of sildenafil in renal ischemia/reperfusion injury in rats

Medeiros, Paulo José de; Neto, Arthur Villarim; Lima, Francisco Pignataro; Azevedo, Ítalo Medeiros; Leão, Layra Ribeiro de Sousa; Medeiros, Aldo Cunha

doi:10.1590/s0102-86502010000600006

Cited by 37 publications

(18 citation statements)

References 24 publications

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“…There was a trend towards a reduction in proinflammatory cytokines in tadalafil treated rats compared to I/R saline group. Besides an overall decreased inflammatory profile, we observed that tadalafil improved fasting plasma urea, creatinine and C-reactive protein levels, and our results correlate with previously published data and known physiological pathways 19,25 . According to the literature, renal ischemia duration of 45 to 75 minutes is most commonly chosen in experimental models, because this ischemia time allows for intermediate survival.…”

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confidence: 91%

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The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats

et al. 2017

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1 1-Experimental SurgeryActa Cir Bras. 2017;32(2):90-97 Abstract Purpose: To evaluate the effect of tadalafil in renal ischemia/reperfusion (I/R) injury in rats. Methods: Group I/R saline rats (n=6) were subjected to 45 minutes of left renal ischemia and treated with saline; the I/R tadalafil rats (n=6) received oral 10mg/kg tadalafil microemulsion one hour before ischemia. In both groups, 8 hours after ischemia, laboratory analysis were performed. Results: Better tissue perfusion was lower in ischemic left/kidney than in right/kidney in saline group, suggesting reduced kidney clearance. Fluorescence in left/kidneys of tadalafil treated rats was lower than in right/kidneys (difference not significant). The fluorescence signal intensity in kidneys of tadafil treated rats was higher than in saline rats. TNF-α levels were significantly lower in I/R tadalafil group rats compared to I/R saline group (154±10.3 vs 391.3±12.3), as well as IL-1β (163.4±13.2 vs 279±11.5pg/dL), and IL-6 (122.9±8.1 vs 173.7±6.3 respectively; p=0.0001). Urea, creatinine and C-reactive protein were significantly lower in tadafil treated rats then in saline group. Conclusion: Tadalafil therapy decreased the expression of circulating pro-inflammatory cytokines in a renal I/R rodent model, while improving kidney function proofs.

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confidence: 91%

“…In a previous study we demonstrated that the pretreatment with sildenafil has a positive effect on I/R of kidneys of rats 19 .…”

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confidence: 87%

The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats

et al. 2017

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“…However, these authors examined the effects of Tadalafil pretreatment (60 min before I/R) on histological changes and oxidative stress in a model of 60 min of ischemia and 60 min of reperfusion without evaluation of kidney function. Similarly, Sildenafil, a short acting member of the PDE5 inhibitor family, was effective in preventing kidney dysfunction and preserving NO bioavailability in an I/R AKI model in rats (6,18,24) and in an experimental postcardiopulmonary bypass-induced AKI (25). The nephroprotective effects of Sildenafil are not restricted to I/R AKI, rather they are also evident in other AKI models such as cisplatin-induced nephrotoxicity (17).…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1

Sohotnik

Nativ

Abbasi

et al. 2013

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

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“…Immediately after the surgical procedure was completed, the rats in the sham-operated and the SLDtreated CLP groups received 10-or 20-mg/kg doses of SLD, which were administered with an oral gavage suspended in saline. There are many sildenafil doses for rats, varying from 0·4 mg/kg to 90 mg/kg, with different administration routes [28][29][30][31][32][33]. The reason we selected 10-and 20-mg/kg doses of oral sildenafil is that 10 mg/kg/day of sildenafil would result approximately in the same plasma concentration as 50 mg in humans [34].…”

Section: Sepsis Modelmentioning

confidence: 99%

Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study

Çadırcı¹,

Halıcı²,

Odabaşoğlu

et al. 2011

Clinical and Experimental Immunology

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SummarySepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD-treated CLP group; (iii) CLP group; and (iv) sham-operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil-treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham-operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)-a level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLPinduced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-a.

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Effect of sildenafil in renal ischemia/reperfusion injury in rats

Abstract: Sildenafil had a protective effect in rat kidneys subjected to normothermic I/R, demonstrated by scintigraphy and histomorphometry.

Cited by 37 publications

References 24 publications

The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats

The renoprotective effect of oral Tadalafil pretreatment on ischemia/reperfusion injury in rats

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1

Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study

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